Choline acetyltransferase as a therapy for hypertension
Compositions and methods are provided comprising choline acetyltransferase (ChAT) and PEGylated ChAT for treating hypertension.
1. A method of reducing systemic hypertension in a subject in need thereof comprising administering to the subject a choline acetyltransferase (ChAT) protein or a ChAT protein conjugated to polyethylene glycol (PEG) in an amount and manner effective to reduce systemic hypertension in a subject,
wherein the subject is an adult human 18 years or older who prior to administration of ChAT protein or PEGylated ChAT protein had a resting systolic blood pressure at or above 130 mmHg and/or a diastolic blood pressure at or above 80 mmHg, and
wherein administration of ChAT protein or PEGylated ChAT protein is effective to reduce systolic blood pressure by 10-40 mmHg.
2. The method of claim 1 , wherein ChAT protein is conjugated to polyethylene glycol (PEG).
3. The method of claim 2 , wherein ChAT protein is conjugated to 2-24 PEG chains.
4. The method of claim 2 , wherein ChAT protein is conjugated to 12 PEG chains.
5. The method of claim 2 , wherein each PEG chain has a molecular weight of 200-2,000 daltons.
6. The method of claim 1 , wherein the subject is an adult human 18 years or older who prior to administration of ChAT protein or PEGylated ChAT protein had a resting systolic blood pressure at or above 140 mmHg and/or a diastolic blood pressure at or above 90 mmHg.
7. The method of claim 1 , wherein the subject has primary hypertension.
8. The method of claim 1 , wherein the subject has secondary hypertension.
9. The method of claim 8 , wherein the subject has narrowing of the arteries and/or chronic kidney disease.
10. The method of claim 1 , wherein ChAT protein or PEGylated ChAT protein is administered by intravenous or intraperitoneal injection or via a pump.
11. The method of claim 1 , wherein ChAT protein or PEGylated ChAT protein is administered by injections or infusions spaced over an interval of one or more days.
12. The method of claim 1 , wherein ChAT protein or PEGylated ChAT protein is chronically administered via a pump.
13. The method of claim 1 , wherein administration of ChAT protein or PEGylated ChAT protein is effective to reduce systolic blood pressure by at least 10 mmHg.
14. The method of claim 1 , wherein administration of ChAT protein or PEGylated ChAT protein is effective to reduce systolic blood pressure by at least 20 mmHg.
15. The method of claim 1 , wherein administration of ChAT protein or PEGylated ChAT protein is effective to reduce systolic blood pressure by at least 30 mmHg.
16. The method of claim 1 , wherein ChAT protein or PEGylated ChAT protein is human recombinant ChAT protein.
17. The method of claim 1 , wherein ChAT protein or PEGylated ChAT protein is ChAT protein isoform R.
18. The method of claim 1 , wherein the subject does not have any one or more of an age-related cognitive disorder, Alzheimer's disease, a neurodegenerative disease, amyotrophic lateral sclerosis, senile dementia, multi-infarct dementia, familial dysautonomia, Huntington's disease, mental retardation, memory loss, myasthenia gravis, a gastrointestinal tract disorder, a spinal cord disorder, a brainstem disorders, a hypothalamic disorder, a limbic system disorder and dementia.